摘要
目的观察apelin-13对离体大鼠缺血/再灌注损伤的影响,并初步探讨其作用机制。方法Langendorff恒流灌注大鼠心脏,采用停灌/复灌方式复制缺血/再灌注模型;观察缺血/再灌注期间心脏收缩期左心室内压上升的最大变化速率(+LVdp/dtmax)及舒张期左心室内压下降的最大变化速率(-LVdp/dtmax);采用比色法检测乳酸脱氢酶(LDH)及超氧化物歧化酶(SOD)活性的变化,Westernblot方法检测内皮型一氧化氮合酶(eNOS)和ERK1/2的表达。结果apelin-13可以增加缺血/再灌注损伤后心脏±dp/dtmax(P<0·01),降低灌流液中LDH水平,增加心肌组织中SOD活性,上调心肌组织中eNOS表达和下调细胞外调节蛋白激酶1和2(ERK1/2)的表达。结论apelin-13拮抗缺血/再灌注引起的心脏收缩及舒张功能障碍及心肌细胞膜稳定性改变;其作用机制可能与增加心肌清除氧自由基的能力、改变eNOS与ERK1/2表达有关。
Aim To observe effects and mechanisms of apelin-13 on ischemia/reperfusion injury in rat heart in virtro. Methods The ischemia/reperfusion models of rat heart in vitro were made through stopping and reperfusion of the KH fluid to the heart; observing changes of maximal rate of the pressure increase （ ＋ dp/dtmax） and maximal rate of the pressure decrease （-dp/dtmax） of heart. Colorimetric method was used to assay the content of lactate dehydrogenase （LDH） and activity of superoxide dismutase （SOD）. Western blot was used to assay endothelial NO synthase （eNOS） and extracellular-regulated kinases （ ERK1/ 2）. Results Groups given low-dosage （30 pmol · L^-1） and high dosage （100 pmol · L^-1） apelin-13 had higher ±LVdp/dtmax （ P 〈 0. 01 ） ; and the leakage of myocardial LDH were attenuated in the group given low-dosage （30 pmol · L^-1 ） apelin-13 ; administration of apelin-13 before and after ischemia/reperfusion resuited in hyper-expression of SOD and eNOS （P 〈 0. 05 ） ,while the expression of ERK1/2 were down regulated （ P 〈 0. 05 ）. Conclusion The protective effects of apelin-13 on ischemia/reperfusion injury in rat heart in vitro may involved in stabilizing the cell membrane of the myocardium, clearing more oxygen-derived free radicals and relaxing the coronary artery.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第1期82-85,共4页
Chinese Pharmacological Bulletin
基金
北京市自然科学基金资助项目(No7062007)
北京市教委基金资助项目(NoKM200510025009)
